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Rubbing Out Fearful Memories

Scientists report that a protein-blocking drug can disrupt specific fearful memories in rats while leaving similar memories intact.

Researchers have long known that memories are first created in a fleeting, short-term form. Some later become more stable through a process called consolidation, which involves the production of new proteins. When long-term memories are recalled, they again become fragile and changeable. New proteins must be produced to reconsolidate these retrieved memories and return them to long-term storage.

Dr. Joseph LeDoux of New York University and his colleagues previously showed that certain drugs can cause rats to lose their conditioned fear of a musical tone. When a tone is repeatedly paired with a mild electric shock to the foot, rats normally remember and respond fearfully to the sound. In their latest study, funded by the NIH National Institute of Mental Health (NIMH), LeDoux and his colleagues set out to see if particular memories could be singled out and selectively disrupted.

As described in a paper published online in Nature Neuroscience on March 11, 2007, the researchers trained rats to fear two different musical tones. They then gave infusions of a drug called U0126, which blocks production of the proteins needed for memory reconsolidation, directly to the brain's fear-processing centers. A half-hour after the infusions, the rats were exposed to one of the tones, but this time without a shock.

The next day, both sounds were replayed for the rats. The treated rats showed no fear of the tone they had heard while under the influence of U0126, yet still reacted with fear to the other tone. Measurements with microelectrodes showed that the rats had significantly reduced electrical responses to the "forgotten" tone in their brain's fear centers compared with the remembered tone.

These findings show that a fearful memory can be targeted and disrupted during reconsolidation, while leaving another fearful memory untouched. U0126 is not approved for human use, but certain prescription drugs — like propranolol — are known to affect memory reconsolidation in humans. Eventually, drugs that disrupt specific recollections may prove useful for the treatment of post-traumatic stress disorder and other memory-related conditions.